Mcl-1 调控NSCLC 对EGFR-TKIs敏感性的实验研究 |
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引用本文: | 李楠,叶明翔,张信信,常宁,张艰.Mcl-1 调控NSCLC 对EGFR-TKIs敏感性的实验研究[J].现代生物医学进展,2016,16(16):3028-3031. |
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作者姓名: | 李楠 叶明翔 张信信 常宁 张艰 |
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作者单位: | 第四军医大学西京医院呼吸科 |
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基金项目: | 国家自然科学基金项目(81272518) |
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摘 要: | 目的:探讨人髓细胞白血病基因-1(myeloid cell leukemia-1,Mcl-1)是否参与调控非小细胞肺癌(non-small cell lung cancer,NSCLC)对EGFR-TKIs的敏感性,为非小细胞肺癌的治疗提供新的思路。方法:通过Western blot方法检测EGFR-TKIs敏感细胞H3255和耐药细胞H1975中Mcl-1蛋白的表达水平。分别给予敏感细胞H3255和耐药细胞H1975 EGFR-TKIs处理后检测细胞凋亡情况和Mcl-1蛋白表达水平。设计并合成特异性si RNA下调耐药细胞H1975中Mcl-1的表达,采用脂质体转染后通过流式细胞技术检测细胞的凋亡情况。结果:H3255细胞Mcl-1表达水平明显低于H1975细胞。一代EGFR-TKIs Gefitinib显著降低H3255细胞Mcl-1表达而不能减少H1975细胞Mcl-1表达。H1975细胞经二代EGFR-TKIs Afatinib和三代EGFR-TKIs AZD9291处理后Mcl-1表达明显减少。特异性si RNA下调H1975细胞Mcl-1表达可以促进细胞凋亡。结论:Mcl-1参与了调节NSCLC对EGFR-TKIs的敏感性,可能成为防止或逆转NSCLC对EGFR-TKIs耐药的潜在靶点。
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关 键 词: | 非小细胞肺癌 人髓细胞白血病基因-1 细胞凋亡 |
Regulation of Mcl-1 on the Sensitivity to EGFR-TKIs of Non-small Cell Lung Cancer |
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Abstract: | Objective:To explore whether myeloid cell leukemia-1 (Mcl-1) participated in regulating the sensitivity to epidermal
growth factor receptor tyrosine kinase inhibitors of non-small cell lung cancer, and provide new ideas for the treatment of non -small cell
lung cancer (NSCLC).Methods:The expression levels of Mcl-1 in EGFR-TKIs sensitive cell H3255 and resistant cell H1975 were
detected by western blot. Then the expression level of Mcl-1 and apoptosis of sensitive cell H3255 and resistant cell H1975 after being
treated with EGFR-TKIs were examined. The specific siRNA that could down-regulate the expression of Mcl-1 in resistant cell H1975
was designed and synthesized, and the apoptosis of these cells wer detected by flow cytometry after liposome transfection.Results:The
expression of Mcl-1 in H3255 cell was significantly lower than that in H1975 cell. Meanwhile, the expression of Mcl-1 prominently
diminished in H3255 cell and the expression of Mcl-1 in H1975 cell had no obvious change in the presence of first generation
EGFR-TKIs Gefitinib. The expression of Mcl-1 was obviously decreased inH1975 cell after being treated with second generation
EGFR-TKIs Afatinib and third generation EGFR-TKIs AZD9291. Flow cytometry showed that specific siRNA which down-regulated the
expression of Mcl-1 in H1975 cell could promote the apoptosis.Conclusion:Mcl-1 participated in regulating the sensitivity to
EGFR-TKIs of NSCLC, and might be regarded as a target to overcome the resistance to EGFR-TKIs of NSCLC. |
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Keywords: | Non-small cell lung cancer Mcl-1 Apoptosis |
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